Introduction: Bilateral myringotomy and tube placement (BMT) is one of the commonest pediatric surgical procedure, but 25% of children may emerge from anesthesia restless, disoriented and combative after this operation. The etiology of this adverse emergence behavior is unclear, though age of < 6 years and the use of sevoflurane, midazolam and atropine may be predisposing factors. Communicating with these children is difficult, but postoperative pain may be another important factor as 70% require analgesics following BMT. (1) Fentanyl, 1-2 mcg/kg IV, has been used effectively to treat postoperative excitement. However, intravenous lines are not routinely inserted during BMT procedures, and other routes of administration of fentanyl are required. The nasal transmucosal route has been used for fentanyl, but there are no data regarding blood levels achieved with this route in children. The aim of this study was to demonstrate if the blood concentration of fentanyl after nasal administration would reach levels known to be associated with adequate analgesia. (2) Methods: In this limited, prospective open label pharmacokinetic study, 26 healthy ASA physical status 1 or 2 children scheduled for BMT surgery were enrolled with IRB approval and parental written informed consent. All subjects received acetaminophen 10mg/kg and midazolam 0.5 mg/kg orally 30 min before induction and maintenance of anesthesia with sevoflurane and nitrous oxide via a face mask. Intranasal fentanyl, 2 mcg/kg, was administered in equal quantities in each nostril after induction, a venous catheter placed and 2 ml of blood drawn at the time of emergence from anesthesia (time 1). A second sample was drawn from this catheter 30 min after arrival in the post anesthesia care unit (time 2). In addition, we assessed postoperative pain and behavior at the time of arrival in the PACU and just before obtaining a second blood sample. We used a validated pain scale (CHEOPS) and a 4-point behavioral scale respectively (1=calm; 2=not calm but could easily be comforted; 3=not easily calmed, moderately agitated or restless; and 4=combative, excited, or disoriented). (2) Blood samples were stored at -70: C until analyzed by a solid-phase radio-immunoassay (RIA) with iodinated tracer (125 I) and antibody coated tubes using a commercially available kit from DPC Inc., LA, CA (3).